Prodrug strategies for antihypertensives

There is a great emphasis on research to discover methods aimed at enhancing the efficacy of drugs and reducing their toxicity and unwanted side effects. Prodrugs are biologically inactive compounds that are converted to actual drug molecule, through biotransformation, that combine with the receptors to produce the biological action. Prodrugs can thus be considered as drugs containing specialized nontoxic protective groups utilized in a transient manner to alter or eliminate the undesirable properties of the parent drug molecule. Hypertension is one of the leading risk factors for cardiovascular disease and represents a major health and economic burden. Most of the drugs for cardiovascular diseases have low oral bioavailability, short duration of action, first pass metabolism and variable lipohilicities. Out of the need to overcome these limitations, various prodrugs have been designed for antihypertensive agents. This review extensively focuses on various strategies used for design and development of prodrugs for the various classes of antihypertensives, emphasizing on the details regarding the need for prodrug synthesis for each class, structure, type of modification and goal achieved. It also provides an insight into the major advances in the field of antihypertensive prodrug research.